The primary purpose of this training grant is to provide rigorous research training for MDs, PhDs and MD/PhDs in cardiovascular biology and medicine with the ultimate goal of preparing trainees as independent clinician-scientists and PhD investigators. The specific rationale underlying the training program is that basic, translational and clinical cardiovascular research requires investigators with a strong foundation in molecular and cellular biology and ultimately formation of multi-disciplinary research collaborations composed ofMD and PhD investigators with complementary expertise. The Penn Cardiovascular Institute provides a unique training environment containing extensive infrastructure used to support multi-disciplinary teams of investigators focused in the strategic areas of CV Development/Congenital Heart Disease, Vascular Biology/Atherosclerosis, Myocyte Biology/Heart Failure, Channel Biology/Electrophysiology and Bioengineering/Molecular Imaging. Support is requested for the continued funding of 6 postdoctoral fellows per year who will perform 2-3 year postdoctoral research fellowships mentored by designated trainers. 28 NIH funded, experienced investigators were chosen as trainers from both clinical and basic science departments at the University of Pennsylvania. Dr. Michael S. Parmacek, Director of the Penn Cardiovascular Institute (CVI), will continue to serve as Director of the training program. Drs H. Lee Sweeney, Chairman of Physiology, and Jonathan A. Epstein, Scientific Director of the Penn CVI, will serve as Co-Directors of the training program. Trainees may choose to enroll in either the Basic Research or Translational/Patient-Oriented Research Track. Specific consideration in each curriculum has been given to the unique aspects of training MD and PhD postdoctoral fellows. The core curriculum will be a well-supervised research preceptorship lasting a minimum of two year. This training will be supplemented by required graduate and medical school classes, lectures, seminars, skill classes (medical writing, obtaining extramural support) and specific courses in the ethical conduct of research. The training program has implemented a formal mentoring system and established an Oversight Committee to monitor trainee progress and the overall goals of the training program. Pre- and postdoctoral trainees for this program will be selected from the Penn Cardiology Fellowship Training program, the Penn Combined Degree Program (MD/PhD) and the Biomedical Graduate Studies (BGS) program. In addition, a strategy to attract individuals from under-represented minorities has been implemented. The inter-departmental structure of this training program provides potential for an unparalleled training environment in cardiovascular research and is aligned directly with the NIH Roadmap. (End of Abstract)